Abstract 2487: Mutation of theSTK11gene predicts recurrence of breast cancer

Introduction: Breast cancer is the most common cancer in women, and some patients develop recurrence after standard therapy. Effective predictors are urgently needed to detect recurrence earlier. Methods: We conducted a comprehensive study via an experimental and bioinformatics approach to detect mutated genes in breast cancer. Twenty-seven breast cancer patients who developed recurrence within 24 months postoperatively and 22 control cancer patients without recurrence were enrolled from National Cheng Kung University Hospital in Taiwan. Targeted deep sequencing was performed to assess the mutations among individuals with breast cancer using a panel of 143 cancer-associated genes. Bioinformatics and public databases were used to predict the protein functions of the mutated genes. Results: Mutations were identified in 49 breast cancer specimens, and the most frequently mutated genes were BRCA2, TP53, APC, ATM, BRCA1, NOTCH1, TET2, NF1, TSC2, PIK3CA, TSC1, PTEN, MSH2, PTCH1, PIK3R1, STK11, RB1, BAP1, CDH1 and FBXW7. Mutation of these genes was correlated with protein phosphorylation and autophosphorylation. Among these highly mutated genes, mutations of STK11 were associated with poor prognosis and increased recurrence of breast cancer. Knockdown of STK11 in triple negative breast cancer cell lines increases transcription of cytokines and modulates immune response. Conclusion: Our findings suggest that mutation of STK11 is correlated with early recurrence of breast cancer patients and it will become a powerful prognostic marker for recurrence of breast cancer. Suppression of STK11 signaling by gene mutation may contribute to immune escape. Citation Format: Chih-Yang Wang, Yung-Chieh Chang, Yao-Lung Kuo, Kuo-Ting Lee, Pai-Sheng Chen, Chun Hei Antonio Cheung, Che-Hung Shen, Chih-Peng Chang, Ming-Derg Lai, Meng-Ru Shen, Hui-Ping Hsu. Mutation of the STK11 gene predicts recurrence of breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2487.